Therapy of severe atopic dermatitis, which is refractory to consistent treatment with topical steroids and topical calcineurin inhibitors is still a problem in many cases. The use of cyclosporine, which is the only approved systemic drug for the therapy of severe atopic dermatitis, is often limited by contraindications or adverse reactions. In this context, results from controlled and open-label studies with novel therapeutic approaches such as methotrexate, omalizumab or rituximab, which are in part very promising, are of great interest. In this work we would like to provide an overview of established and new therapeutic options for the treatment of severe atopic dermatitis.